The overall objective of this project is to extend the capabilities of implanted neuroprostheses for restoring lower extremity function after spinal cord injury (SCI) beyond simple standing to include brace-free reciprocal stepping. We will accomplish this by developing and deploying new nerve cuff electrodes designed specifically for the compound femoral and sciatic nerves. Nerve-based approaches offer several distinct advantages over muscle-based electrodes currently utilized in implanted functional electrical stimulation (FES) systems. In this continuing investigation, we will 1) perform acute and chronic testing of the Flat Interface Nerve Electrode (FINE) configured specifically for the proximal femoral nerve, 2) demonstrate the clinical utility of the FINE in implanted neuroprostheses for standing and stepping after paralysis, 3) design and validate new configurations of the FINE for the human sciatic nerve to control ankle motion, and 4) exploit the fascicular selectivity of these new neural interfaces to extend the capabilities of the implanted neuroprosthesis to include brace-free standing and energy efficient reciprocal stepping. We will accomplish these objectives through our proven methodology for translational research consisting of quantitative neuroanatomical studies of peripheral nerve fascicular structure, theoretical optimization of electrode design via innovative combinations of neural and musculoskeletal modeling, by design validation through acute intraoperative testing, and chronic implantation and experimental demonstration of clinical performance. At the conclusion of this phase of the project we will have established the viability of a new class of biologically inspired and rigorously engineered neural interfaces that expand the functional abilities of their users beyond what is currently achievable with existing muscle-based alternatives. The Specific Aims of the project are: 1) Verify operation of the FINE designed for the proximal femoral nerve and characterize its recruitment properties in acute human trials;2) Determine chronic clinical performance of neuroprostheses incorporating the proximal femoral FINE and compare to historical controls utilizing other electrode technologies;3) Establish feasibility of selective activation of the ankle musculature via multicontact nerve cuff electrodes on the lower sciatic nerve;and 4) Verify the long-term operation of the FINE designed to control the ankle muscles and characterize their clinical performance in chronic human trials.Completion of this project will represent a significant advancement in the state of the art of motor system neuroprostheses. It will extend the functionality of neuroprostheses currently undergoing clinical trials, provide immediate benefit to existing system users, and expand the options available to include stepping. Just as importantly, selective activation of individual muscles from a single multi-contact cuff electrode around a multi-fascicular nerve trunk will simplify surgical installation of these systems. Thus, the proposed studies continue to build a foundation for new developments in lower extremity neuroprostheses while making cutting edge technologies available to individuals with paralysis through our proven methodology for translating fundamental discovery in the laboratory to chronic clinical application.